Effect of Cangrelor on Infarct Size in ST-Segment Elevation Myocardial Infarction Treated By Primary Percutaneous Coronary Intervention: A Randomized Controlled Trial (The PITRI Trial).

Background: The administration of intravenous cangrelor at reperfusion achieves faster onset of platelet P2Y12 inhibition than oral ticagrelor and has been shown to reduce myocardial infarct (MI) size in the pre-clinical setting. We hypothesized that the administration of cangrelor at reperfusion will reduce MI size and prevent microvascular obstruction (MVO) in patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI). Methods: This was a Phase 2, multi-center, randomized, double-blind, placebo controlled clinical trial conducted between November 2017 to November 2021 in six cardiac centers in Singapore (NCT03102723). Patients were randomized to receive either cangrelor or placeboinitiated prior to the PPCI procedure on top of oral ticagrelor. The key exclusion criteria included: presenting <6 hours of symptom onset, prior MI and stroke or transient ischemic attack; on concomitant oral anticoagulants; and a contraindication for cardiovascular magnetic resonance (CMR). The primary efficacy endpoint was acute MI size by CMR within the first week expressed as percentage of the left ventricle mass ( %LVmass). MVO was identified as areas of dark core of hypoenhancement within areas of late gadolinium enhancement. The primary safety endpoint was Bleeding Academic Research Consortium (BARC)-defined major bleeding in the first 48 hours. Continuous variables were compared by Mann-Whitney U test [reported as median (1st quartile- 3rd quartile)] and categorical variables were compared by Fisher's exact test. A 2-sided P<0.05 was considered statistically significant. Results: Of 209 recruited patients, 164 patients (78% ) completed the acute CMR scan. There were no significant differences in acute MI size [placebo: 14.9 (7.3 - 22.6) %LVmass versus cangrelor: 16.3 (9.9 - 24.4)%LVmass, P=0.40] or the incidence [placebo: 48% versus cangrelor: 47%, P=0.99] and extent of MVO [placebo:1.63 (0.60 - 4.65)%LVmass versus cangrelor: 1.18 (0.53 - 3.37)%LVmass, P=0.46] between placebo and cangrelor despite a two-fold decrease in platelet reactivity with cangrelor. There were no BARC-defined major bleeding events in either group in the first 48 hours. Conclusions: Cangrelor administered at time of PPCI did not reduce acute MI size or prevent MVO in STEMI patients given oral ticagrelor despite a significant reduction of platelet reactivity during the PCI procedure.

Inflammatory risk contributes to post-COVID endothelial dysfunction through anti-ACKR1 autoantibody.

Subclinical vascular impairment can be exacerbated in individuals who experience sustained inflammation after COVID-19 infection. Our study explores the prevalence and impact of autoantibodies on vascular dysfunction in healthy COVID-19 survivors, an area that remains inadequately investigated. Focusing on autoantibodies against the atypical chemokine receptor 1 (ACKR1), COVID-19 survivors demonstrated significantly elevated anti-ACKR1 autoantibodies, correlating with systemic cytokines, circulating damaged endothelial cells, and endothelial dysfunction. An independent cohort linked these autoantibodies to increased vascular disease outcomes during a median 6.7-yr follow-up. We analyzed a single-cell transcriptome atlas of endothelial cells from diverse mouse tissues, identifying enriched Ackr1 expressions in venous regions of the brain and soleus muscle vasculatures, which holds intriguing implications for tissue-specific venous thromboembolism manifestations reported in COVID-19. Functionally, purified immunoglobulin G (IgG) extracted from patient plasma did not trigger cell apoptosis or increase barrier permeability in human vein endothelial cells. Instead, plasma IgG enhanced antibody-dependent cellular cytotoxicity mediated by patient PBMCs, a phenomenon alleviated by blocking peptide or liposome ACKR1 recombinant protein. The blocking peptide uncovered that purified IgG from COVID-19 survivors possessed potential epitopes in the N-terminal extracellular domain of ACKR1, which effectively averted antibody-dependent cellular cytotoxicity. Our findings offer insights into therapeutic development to mitigate autoantibody reactivity in blood vessels in chronic inflammation.

Mandibular Advancement vs CPAP for Blood Pressure Reduction in Patients With Obstructive Sleep Apnea.

BACKGROUND: Hypertension guidelines recommend diagnosis and treatment of obstructive sleep apnea (OSA) in patients with hypertension. The mandibular advancement device (MAD) is an oral appliance therapy for patients who decline or cannot tolerate continuous positive airway pressure (CPAP). OBJECTIVES: We compared the relative effectiveness of MAD vs CPAP in reducing 24-hour ambulatory blood pressure (BP). METHODS: In an investigator-initiated, randomized, noninferiority trial (prespecified margin 1.5 mm Hg), 321 participants aged ≥40 years with hypertension and increased cardiovascular risk were recruited at 3 public hospitals for polysomnography. Of these, 220 participants with moderate-to-severe OSA (apnea-hypopnea index ≥15 events per hour) were randomized to either MAD or CPAP (1:1). The primary outcome was the difference between the 24-hour mean arterial BP at baseline and 6 months. RESULTS: Compared with baseline, the 24-hour mean arterial BP decreased by 2.5 mm Hg (P = 0.003) at 6 months in the MAD group, whereas no change was observed in the CPAP group (P = 0.374). The between-group difference was -1.6 mm Hg (95% CI: -3.51 to 0.24, noninferiority P < 0.001). The MAD group demonstrated a larger between-group reduction in all secondary ambulatory BP parameters compared with the CPAP group, with the most pronounced effects observed in the asleep BP parameters. Both the MAD and CPAP improved daytime sleepiness, with the between-group difference similar (P = 0.384). There were no between-group differences in cardiovascular biomarkers. CONCLUSIONS: MAD is noninferior to CPAP for reducing 24-hour mean arterial BP in participants with hypertension and increased cardiovascular risk. (Cardiosleep Research Program on Obstructive Sleep Apnea, Blood Pressure Control and Maladaptive Myocardial Remodeling-Non-inferiority Trial [CRESCENT]; NCT04119999).

Use of wearable technology in cardiac monitoring after cryptogenic stroke or embolic stroke of undetermined source: a systematic review.

INTRODUCTION: Prolonged cardiac monitoring after cryptogenic stroke or embolic stroke of undetermined source (ESUS) is necessary to identify atrial fibrillation (AF) that requires anticoagulation. Wearable devices may improve AF detection compared to conventional management. We aimed to review the evidence for the use of wearable devices in post-cryptogenic stroke and post-ESUS monitoring. METHODS: We performed a systematic search of PubMed, EMBASE, Scopus and clinicaltrials.gov on 21 July 2022, identifying all studies that investigated the use of wearable devices in patients with cryptogenic stroke or ESUS. The outcomes of AF detection were analysed. Literature reports on electrocardiogram (ECG)-based (external wearable, handheld, patch, mobile cardiac telemetry [MCT], smartwatch) and photoplethysmography (PPG)-based (smartwatch, smartphone) devices were summarised. RESULTS: A total of 27 relevant studies were included (two randomised controlled trials, seven prospective trials, 10 cohort studies, six case series and two case reports). Only four studies compared wearable technology to Holter monitoring or implantable loop recorder, and these studies showed no significant differences on meta-analysis (odds ratio 2.35, 95% confidence interval [CI] 0.74-7.48, I 2 = 70%). External wearable devices detected AF in 20.7% (95% CI 14.9-27.2, I 2 = 76%) of patients and MCT detected new AF in 9.6% (95% CI 7.4%-11.9%, I 2 = 56%) of patients. Other devices investigated included patch sensors, handheld ECG recorders and PPG-based smartphone apps, which demonstrated feasibility in the post-cryptogenic stroke and post-ESUS setting. CONCLUSION: Wearable devices that are ECG or PPG based are effective for paroxysmal AF detection after cryptogenic stroke and ESUS, but further studies are needed to establish how they compare with Holter monitors and implantable loop recorder.

Left Ventricular Diastolic Dysfunction Is Associated with Poor Functional Outcomes after Endovascular Thrombectomy.

INTRODUCTION: With the advent of endovascular thrombectomy (ET), patients with acute ischaemic strokes (AIS) with large vessel occlusion (LVO) have seen vast improvements in treatment outcomes. Left ventricular diastolic dysfunction (LVDD) has been shown to herald poorer prognosis in conditions such as myocardial infarction. However, whether LVDD is related to functional recovery and outcomes in ischaemic stroke remains unclear. We studied LVDD for possible relation with clinical outcomes in patients with LVO AIS who underwent ET. METHODS: We studied a retrospective cohort of 261 LVO AIS patients who had undergone ET at a single comprehensive stroke centre and correlated LVDD to short-term mortality (in-hospital death) as well as good functional recovery defined as modified Rankin Scale of 0-2 at 3 months. RESULTS: The study population had a mean age of 65-years-old and were predominantly male (54.8%). All of the patients underwent ET with 206 (78.9%) achieving successful reperfusion. Despite this, 25 (9.6%) patients demised during the hospital admission and 149 (57.1%) did not have good function recovery at 3 months. LVDD was present in 82 (31.4%) patients and this finding indicated poorer outcomes in terms of functional recovery at 3 months (OR 2.18, 95% CI 1.04-4.54, p = 0.038) but was not associated with increased in-hospital mortality (OR 2.18, 95% CI 0.60-7.99, p = 0.240) after adjusting for various confounders. CONCLUSION: In addition to conventional echocardiographic indices such as left ventricular ejection fraction, LVDD may portend poorer outcomes after ET, and this relationship should be investigated further.

Remote intensive management to improve antiplatelet adherence in acute myocardial infarction: a secondary analysis of the randomized controlled IMMACULATE trial.

This study aim to investigate if remote intensive coaching for the first 6 months post-AMI will improve adherence to the twice-a-day antiplatelet medication, ticagrelor. Between July 8, 2015, to March 29, 2019, AMI patients were randomly assigned to remote intensive management (RIM) or standard care (SC). RIM participants underwent 6 months of weekly then two-weekly consultations to review medication side effects and medication adherence coaching by a centralized nurse practitioner team, whereas SC participants received usual cardiologist face-to-face consultations. Adherence to ticagrelor were determined using pill counting and serial platelet reactivity measurements for 12 months. A total of 149 (49.5%) of participants were randomized to RIM and 152 (50.5%) to SC. Adherence to ticagrelor was similar between RIM and SC group at 1 month (94.4 ± 0.7% vs. 93.6±14.7%, p = 0.537), 6 months (91.0±14.6% vs. 90.6±14.8%, p = 0.832) and 12 months (87.4±17.0% vs. 89.8±12.5%, p = 0.688). There was also no significant difference in platelet reactivity between the RIM and SC groups at 1 month (251AU*min [212-328] vs. 267AU*min [208-351], p = 0.399), 6 months (239AU*min [165-308] vs. 235AU*min [171-346], p = 0.610) and 12 months (249AU*min [177-432] vs. 259AU*min [182-360], p = 0.678). Sensitivity analysis did not demonstrate any association of ticagrelor adherence with bleeding events and major adverse cardiovascular events. RIM, comprising 6 months of intensive coaching by nurse practitioners, did not improve adherence to the twice-a-day medication ticagrelor compared with SC among patients with AMI. A gradual decline in ticagrelor adherence over 12 months was observed despite 6 months of intensive coaching.

Efficacy and safety of tirzepatide, GLP-1 receptor agonists, and other weight loss drugs in overweight and obesity: a network meta-analysis.

OBJECTIVE: This network meta-analysis evaluates the efficacy and safety of tirzepatide compared to glucagon-like peptide-1 receptor agonists (GLP-1 RA) and other weight loss drugs in the treatment of overweight and obesity. METHODS: MEDLINE, Embase, and Cochrane CENTRAL were searched for randomized controlled trials on tirzepatide, GLP-1 RA, and weight loss drugs approved by the US Food and Drug Administration. A network meta-analysis was performed, drawing direct and indirect comparisons between treatment groups. Network diagrams and surface under the cumulative ranking curve analysis were performed for primary (≥5%, ≥10%, ≥15%, absolute weight loss) and secondary outcomes and adverse effects. RESULTS: Thirty-one randomized controlled trials, involving more than 35,000 patients, were included in this study. Tirzepatide 15 mg ranked in the top three across weight-related parameters, glycemic profile (glycated hemoglobin), lipid parameters (total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides), and blood pressure. Tirzepatide 15 mg had the highest efficacy compared with placebo for achieving ≥15% weight loss (risk ratio 10.24, 95% CI: 6.42-16.34). As compared to placebo, tirzepatide and GLP-1 RA across all doses had significant increases in gastrointestinal adverse effects. CONCLUSIONS: The superiority of tirzepatide and GLP-1 RA in inducing weight loss and their ability to target multiple metabolic parameters render them promising candidates in the treatment of patients with overweight and obesity.

CURATE.AI-assisted dose titration for anti-hypertensive personalized therapy: study protocol for a multi-arm, randomized, pilot feasibility trial using CURATE.AI (CURATE.AI ADAPT trial).

Aims: Artificial intelligence-driven small data platforms such as CURATE.AI hold potential for personalized hypertension care by assisting physicians in identifying personalized anti-hypertensive doses for titration. This trial aims to assess the feasibility of a larger randomized controlled trial (RCT), evaluating the efficacy of CURATE.AI-assisted dose titration intervention. We will also collect preliminary efficacy and safety data and explore stakeholder feedback in the early design process. Methods and results: In this open-label, randomized, pilot feasibility trial, we aim to recruit 45 participants with primary hypertension. Participants will be randomized in 1:1:1 ratio into control (no intervention), home blood pressure monitoring (active control; HBPM), or CURATE.AI arms (intervention; HBPM and CURATE.AI-assisted dose titration). The home treatments include 1 month of two-drug anti-hypertensive regimens. Primary endpoints assess the logistical (e.g. dose adherence) and scientific (e.g. percentage of participants for which CURATE.AI profiles can be generated) feasibility, and define the progression criteria for the RCT in a 'traffic light system'. Secondary endpoints assess preliminary efficacy [e.g. mean change in office blood pressures (BPs)] and safety (e.g. hospitalization events) associated with each treatment protocol. Participants with both baseline and post-treatment BP measurements will form the intent-to-treat analysis. Following their involvement with the CURATE.AI intervention, feedback from CURATE.AI participants and healthcare providers will be collected via exit survey and interviews. Conclusion: Findings from this study will inform about potential refinements of the current treatment protocols before proceeding with a larger RCT, or potential expansion to collect additional information. Positive results may suggest the potential efficacy of CURATE.AI to improve BP control. Trial registration number: NCT05376683.

Predictors of major adverse cardiac events among patients with chest pain and low HEART score in the emergency department.

AIM: For patients who present to the emergency departments (ED) with undifferentiated chest pain, the risk of major adverse cardiac events (MACE) may be underestimated in low-HEART score patients. We aimed to identify characteristics of patients who were classified as low risk by HEART score but subsequently developed MACE at 6 weeks. METHODS: We studied a multiethnic cohort of patients who presented with chest pain arousing suspicion of acute coronary syndrome to EDs in the Netherlands and Singapore. Patients were risk-stratified using HEART score and followed up for MACE at 6 weeks. Risk factors of developing MACE despite low HEART scores (scores 0-3) were identified using logistic and Cox regression models. RESULTS: Among 1376 (39.8%) patients with low HEART scores, 63 (4.6%) developed MACE at 6 weeks. More males (53/806, 6.6%) than females (10/570, 2.8%) with low HEART score developed MACE. There was no difference in outcomes between ethnic groups. Among low-HEART score patients with 2 points for history, 21% developed MACE. Among low-HEART score patients with 1 point for troponin, 50% developed MACE, while 100% of those with 2 points for troponin developed MACE. After adjusting for HEART score and potential confounders, male sex was independently associated with increased odds (OR 4.12, 95%CI 2.14-8.78) and hazards (HR 3.93, 95%CI 1.98-7.79) of developing MACE despite low HEART score. CONCLUSION: Male sex, highly suspicious history and elevated troponin were disproportionately associated with MACE. These characteristics should prompt clinicians to consider further investigation before discharge.

Non-Vitamin K Antagonist Oral Anticoagulants versus Low Molecular Weight Heparin for Cancer-Related Venous Thromboembolic Events: Individual Patient Data Meta-Analysis.

Venous thromboembolism (VTE) is a leading cause of morbidity and mortality in cancer patients. Low molecular weight heparin (LMWH) has been the standard of care but new guidelines have approved the use of non-vitamin K antagonist oral anticoagulants (NOAC). By conducting an individual patient data (IPD) meta-analysis of randomised controlled trials (RCTs) comparing the outcomes of NOAC versus LMWH in cancer patients, we aim to determine an ideal strategy for the prophylaxis of VTE and prevention of VTE recurrence. Three databases were searched from inception until 19 October 2022. IPD was reconstructed from Kaplan-Meier curves. Shared frailty, stratified Cox and Royston-Parmar models were fit to compare the outcomes of venous thromboembolism recurrence and major bleeding. For studies without Kaplan-Meier curves, aggregate data meta-analysis was conducted using random-effects models. Eleven RCTs involving 4844 patients were included. Aggregate data meta-analysis showed that administering NOACs led to a significantly lower risk of recurrent VTE (RR = 0.65; 95%CI: 0.50-0.84) and deep vein thrombosis (DVT) (RR = 0.60; 95%CI: 0.40-0.90). In the IPD meta-analysis, NOAC when compared with LMWH has an HR of 0.65 (95%CI: 0.49-0.86) for VTE recurrence. Stratified Cox and Royston-Parmar models demonstrated similar results. In reducing risks of recurrent VTE and DVT among cancer patients, NOACs are superior to LMWHs without increased major bleeding.

Global Registry of Acute Coronary Events Score Underestimates Post-Acute Coronary Syndrome Mortality among Cancer Patients.

Background Patients with prior cancer are at increased risk of acute coronary syndrome (ACS) with poorer post-ACS outcomes. We aimed to ascertain if the Global Registry of Acute Coronary Events (GRACE) score accurately predicts mortality risk among patients with ACS and prior cancer. Methods We linked nationwide ACS and cancer registries from 2007 to 2018 in Singapore. A total of 24,529 eligible patients had in-hospital and 1-year all-cause mortality risk calculated using the GRACE score (2471 prior cancer; 22,058 no cancer). Results Patients with prior cancer had two-fold higher all-cause mortality compared to patients without cancer (in-hospital: 22.8% versus 10.3%, p < 0.001; 1-year: 49.0% vs. 18.7%, p < 0.001). Cardiovascular mortality did not differ between groups (in-hospital: 5.2% vs. 4.8%, p = 0.346; 1-year: 6.9% vs. 6.1%, p = 0.12). The area under the receiver operating characteristic curve of the GRACE score for prediction of all-cause mortality was less for prior cancer (in-hospital: 0.64 vs. 0.80, p < 0.001; 1-year: 0.66 vs. 0.83, p < 0.001). Among patients with prior cancer and a high-risk GRACE score > 140, in-hospital revascularization was not associated with lower cardiovascular mortality than without in-hospital revascularization (6.7% vs. 7.6%, p = 0.50). Conclusions The GRACE score performs poorly in risk stratification of patients with prior cancer and ACS.

Targeted Plasma Metabolomics Reveals Association of Acute Myocardial Infarction Risk with the Dynamic Balance between Trimethylamine-N-oxide, Betaine, and Choline.

The relationship between trimethylamine-N-oxide (TMAO), betaine, and choline with acute myocardial infarction (AMI) end point remains unclear. We analyzed plasma TMAO, betaine, and choline concentrations in AMI cases and non-AMI community-dwelling controls by LC-MS/MS to understand how the balance between these metabolites helps to reduce AMI risk. Results showed that the odds ratio (OR) for the highest versus lowest quartiles of betaine was 0.30 (95% CI, 0.10-0.82) after adjustment for AMI risk factors, and the unadjusted OR for quartile 3 versus quartile 1 of TMAO was 2.47 (95% CI, 1.02-6.17) (p < 0.05). The study populations with "high betaine + low TMAO" had a significant protective effect concerning AMI with a multivariable-adjusted OR of 0.20 (95% CI, 0.07-0.55) (p < 0.01). Multivariate linear regression showed that the chronological age was correlated with TMAO concentrations among AMI patients (95% CI, 0.05-3.24, p < 0.01) but not among the controls. This implies a further potential interplay between age and metabolite combination─AMI risk association.

What's the optimal duration of anticoagulation in patients with left ventricular thrombus?

INTRODUCTION: Left ventricular thrombus (LVT) occurs in acute myocardial infarction and in ischemic and non-ischemic cardiomyopathies. LVT may result in embolic stroke. Currently, the duration of anticoagulation for LVT is unclear. This is an important clinical question as prolonged anticoagulation is associated with increased bleeding risks, while premature discontinuation may result in embolic complications. AREAS COVERED: There are no randomized trial data regarding anticoagulation duration for LVT. Guidelines and expert consensus recommend anticoagulation for 3-6 months with cessation of anticoagulation if interval imaging demonstrates thrombus resolution. Cardiac magnetic resonance imaging (CMR) is more sensitive and specific compared to echocardiography for LVT detection, and may be appropriate for high-risk patients. Prolonged anticoagulation may be considered in unresolved protuberant or mobile LVT, and in patients with resolved LVT but persistent depressed left ventricular ejection fraction and/or myocardial akinesia or dyskinesia. EXPERT OPINION: CMR will likely be increasingly used for LVT surveillance to guide anticoagulation duration. Further research is needed to determine which patients with persistent LVT on CMR benefit from prolonged anticoagulation.

Association Between Calcium Supplementation and the Risk of Cardiovascular Disease and Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Some observational studies and randomised controlled trials (RCTs) have reported an association between calcium supplementation and increased risk of cardiovascular disease. Previous meta-analyses on the topic, based on data from RCTs and observational studies, have contradictory findings. This meta-analysis was conducted to determine the difference in associated risks of calcium supplementation with cardiovascular disease and stroke in RCTs. METHODS: Relevant studies published from database inception to 6 August 2021 were sourced from PubMed, Embase, Scopus, and the Cochrane Central Register of Controlled Trials. Any RCTs focusing on the relationship between calcium supplementation and incidence of cardiovascular disease or stroke were included. Articles were screened independently by two authors, according to the PICO criteria, with disagreements resolved by a third author. RESULTS: Twelve RCTs were included in the meta-analysis. Calcium supplementation was not associated with myocardial infarction, total stroke, heart failure admission, and all-cause/cardiovascular mortality. Subgroup analysis focusing on calcium monotherapy/calcium co-therapy with vitamin D, female sex, follow-up duration, and geographical region did not affect the findings. CONCLUSION: Calcium supplementation was not associated with myocardial infarction, total stroke, heart failure admission, and cardiovascular/all-cause mortality. Further studies are required to examine and understand these associations.

Trends and predictions of metabolic risk factors for acute myocardial infarction: findings from a multiethnic nationwide cohort.

Background: Understanding the trajectories of metabolic risk factors for acute myocardial infarction (AMI) is necessary for healthcare policymaking. We estimated future projections of the incidence of metabolic diseases in a multi-ethnic population with AMI. Methods: The incidence and mortality contributed by metabolic risk factors in the population with AMI (diabetes mellitus [T2DM], hypertension, hyperlipidemia, overweight/obesity, active/previous smokers) were projected up to year 2050, using linear and Poisson regression models based on the Singapore Myocardial Infarction Registry from 2007 to 2018. Forecast analysis was stratified based on age, sex and ethnicity. Findings: From 2025 to 2050, the incidence of AMI is predicted to rise by 194.4% from 482 to 1418 per 100,000 population. The largest percentage increase in metabolic risk factors within the population with AMI is projected to be overweight/obesity (880.0% increase), followed by hypertension (248.7% increase), T2DM (215.7% increase), hyperlipidemia (205.0% increase), and active/previous smoking (164.8% increase). The number of AMI-related deaths is expected to increase by 294.7% in individuals with overweight/obesity, while mortality is predicted to decrease by 11.7% in hyperlipidemia, 29.9% in hypertension, 32.7% in T2DM and 49.6% in active/previous smokers, from 2025 to 2050. Compared with Chinese individuals, Indian and Malay individuals bear a disproportionate burden of overweight/obesity incidence and AMI-related mortality. Interpretation: The incidence of AMI is projected to continue rising in the coming decades. Overweight/obesity will emerge as fastest-growing metabolic risk factor and the leading risk factor for AMI-related mortality. Funding: This research was supported by the NUHS Seed Fund (NUHSRO/2022/058/RO5+6/Seed-Mar/03) and National Medical Research Council Research Training Fellowship (MOH-001131). The SMIR is a national, ministry-funded registry run by the National Registry of Diseases Office and funded by the Ministry of Health, Singapore.

Acute Myocardial Infarction and Risk of Cognitive Impairment and Dementia: A Review.

Cognitive impairment (CI) shares common cardiovascular risk factors with acute myocardial infarction (AMI), and is increasingly prevalent in our ageing population. Whilst AMI is associated with increased rates of CI, CI remains underreported and infrequently identified in patients with AMI. In this review, we discuss the evidence surrounding AMI and its links to dementia and CI, including pathophysiology, risk factors, management and interventions. Vascular dysregulation plays a major role in CI, with atherosclerosis, platelet activation, microinfarcts and perivascular inflammation resulting in neurovascular unit dysfunction, disordered homeostasis and a dysfunctional neurohormonal response. This subsequently affects perfusion pressure, resulting in enlarged periventricular spaces and hippocampal sclerosis. The increased platelet activation seen in coronary artery disease (CAD) can also result in inflammation and amyloid-ß protein deposition which is associated with Alzheimer's Dementia. Post-AMI, reduced blood pressure and reduced left ventricular ejection fraction can cause chronic cerebral hypoperfusion, cerebral infarction and failure of normal circulatory autoregulatory mechanisms. Patients who undergo coronary revascularization (percutaneous coronary intervention or bypass surgery) are at increased risk for post-procedure cognitive impairment, though whether this is related to the intervention itself or underlying cardiovascular risk factors is debated. Mortality rates are higher in dementia patients with AMI, and post-AMI CI is more prevalent in the elderly and in patients with post-AMI heart failure. Medical management (antiplatelet, statin, renin-angiotensin system inhibitors, cardiac rehabilitation) can reduce the risk of post-AMI CI; however, beta-blockers may be associated with functional decline in patients with existing CI. The early identification of those with dementia or CI who present with AMI is important, as subsequent tailoring of management strategies can potentially improve outcomes as well as guide prognosis.

Association Between Breast Arterial Calcifications and Cardiovascular Disease: A Systematic Review and Meta-analysis.

BACKGROUND: Recent studies have shown that breast arterial calcification (BAC) detected on screening mammography is linked to cardiovascular diseases via medial calcification. However, its effect on cardiovascular outcomes remains unclear. Therefore, we conducted a meta-analysis to determine the effect of BAC on cardiovascular outcomes in patients. METHODS: Three electronic databases (Pubmed, Embase, and Scopus) were searched on May 1, 2022, for studies examining the relationship between BAC and cardiovascular outcomes including cardiac death, acute myocardial infarction, ischemic heart disease, stroke, peripheral artery disease, and heart failure. A random-effects meta-analysis model was used to summarise the studies. RESULTS: A total of 5 longitudinal studies were included with a combined cohort of 87,865 patients. Significantly, the pooled risk ratio (RR) of the association between BAC and cardiac death was 2.06 (P < 0.00001). BAC was associated with a significantly increased risk of developing other cardiovascular diseases, such as ischemic/hemorrhagic stroke (RR 1.51; P = 0.003), ischemic stroke (RR 1.82; P < 0.00001), peripheral vascular disease (RR 1.24; P = 0.003), and heart failure (RR 1.84; P < 0.00001). There was no significant relationship for developing myocardial infarction or for total cardiovascular diseases. CONCLUSIONS: Our findings suggest that BAC was associated with an increased risk of cardiovascular mortality, and certain cardiovascular outcomes. There is thus a potential to use BAC as a sex-specific cardiovascular risk assessment tool. Furthermore, there is a need for more widespread reporting of BAC to better understand the pathophysiologic mechanisms behind its correlation with cardiovascular disease and to apply it in clinical practice.

Left Ventricular Ejection Fraction Association with Acute Ischemic Stroke Outcomes in Patients Undergoing Thrombolysis.

(1) Background: Little is known about how left ventricular systolic dysfunction (LVSD) affects functional and clinical outcomes in acute ischemic stroke (AIS) patients undergoing thrombolysis; (2) Methods: A retrospective observational study conducted between 2006 and 2018 included 937 consecutive AIS patients undergoing thrombolysis. LVSD was defined as left ventricular ejection fraction (LVEF) < 50%. Univariate and multivariate binary logistic regression analysis was performed for demographic characteristics. Ordinal shift regression was used for functional modified Rankin Scale (mRS) outcome at 3 months. Survival analysis of mortality, heart failure (HF) admission, myocardial infarction (MI) and stroke/transient ischemic attack (TIA) was evaluated with a Cox-proportional hazards model; (3) Results: LVSD patients in comparison with LVEF ≥ 50% patients accounted for 190 and 747 patients, respectively. LVSD patients had more comorbidities including diabetes mellitus (100 (52.6%) vs. 280 (37.5%), p < 0.001), atrial fibrillation (69 (36.3%) vs. 212 (28.4%), p = 0.033), ischemic heart disease (130 (68.4%) vs. 145 (19.4%), p < 0.001) and HF (150 (78.9%) vs. 46 (6.2%), p < 0.001). LVSD was associated with worse functional mRS outcomes at 3 months (adjusted OR 1.41, 95% CI 1.03-1.92, p = 0.030). Survival analysis identified LVSD to significantly predict all-cause mortality (adjusted HR [aHR] 3.38, 95% CI 1.74-6.54, p < 0.001), subsequent HF admission (aHR 4.23, 95% CI 2.17-8.26, p < 0.001) and MI (aHR 2.49, 95% CI 1.44-4.32, p = 0.001). LVSD did not predict recurrent stroke/TIA (aHR 1.15, 95% CI 0.77-1.72, p = 0.496); (4) Conclusions: LVSD in AIS patients undergoing thrombolysis was associated with increased all-cause mortality, subsequent HF admission, subsequent MI and poorer functional outcomes, highlighting a need to optimize LVEF.

Efficacy and safety of tirzepatide for treatment of overweight or obesity. A systematic review and meta-analysis.

BACKGROUND: Recent studies suggest that tirzepatide, a dual glucose-dependent insulinotropic-peptide (GIP) and glucagon-like peptide-1 receptor agonist (GLP-1 RA), has significant weight loss effects. This systematic review and meta-analysis aims to assess the efficacy and safety of tirzepatide for weight loss in patients with overweight or obesity. METHODS: Medline, Embase and Cochrane CENTRAL were searched for randomized controlled trials (RCTs) on tirzepatide's weight loss efficacy for these patients. A single arm meta-analysis of proportions estimated primary outcomes, ≥5%, ≥10%, and ≥15% weight loss, and adverse events (AEs); while meta-analysis of means estimated secondary outcomes. Comparative meta-analysis was conducted between tirzepatide and control arms where mean differences and odds ratios were estimated for continuous and dichotomous outcomes respectively. RESULTS: RCTs included in this study revealed that among 5800 patients, 78.22% (95% CI: 72.15% to 83.73%), 55.60% (95% CI: 46.54% to 64.47%), 32.28% (95% CI: 23.17% to 42.12%) achieved ≥5%, ≥10%, and ≥15% weight loss, respectively. Tirzepatide 5 mg demonstrated weight loss superiority relative to placebo (MD: -12.47 kg, 95% CI: -13.94 kg to -11.00 kg) and semaglutide (n = 1409, MD: -1.90 kg, 95% CI: -2.97 kg to -0.83 kg) with dose-dependent increase for 10 mg and 15 mg doses. The comparison between tirzepatide and semaglutide was examined in the SURPASS-2 trial that was included in this systematic review. For AEs, there was increase odds of experiencing gastrointestinal AEs with tirzepatide compared to placebo, but no significant difference with semaglutide. CONCLUSION: Tirzepatide has significant potential as a weight loss drug in patients with overweight and obesity, with little increase in AEs compared to other weight loss drugs. With its ability to concurrently target multiple aspects of metabolic syndrome, it should be considered as the next helm of weight loss therapies.

Higher risk of adverse cardiovascular outcomes in females with type 2 diabetes Mellitus: an Umbrella review of systematic reviews.

BACKGROUND: Previous studies have shown that females with type 2 diabetes mellitus (T2DM) may have excess mortality risk compared to their male counterparts. An important next step to address the high global burden of T2DM and cardiovascular disease (CVD) is an umbrella review to summarize data on sex differences in cardiovascular outcomes for patients with T2DM and assess the strength of the evidence observed. METHODS AND RESULTS: Medline and Embase were searched from inception till 7 August 2022 for systematic reviews and meta-analyses studying the effects of sex on cardiovascular outcomes in T2DM patients. Results from reviews were synthesized with a narrative synthesis, with a tabular presentation of findings and forest plots for reviews that performed a meta-analysis. 27 review articles evaluating sex differences in cardiovascular outcomes were included. Females with T2DM had a higher risk of developing coronary heart disease (CHD; RRR: 1.52, 95%CI: 1.32-1.76, P < 0.001), acute coronary syndrome (ACS; RRR: 1.38, 95%CI: 1.25-1.52, P < 0.001), heart failure (RRR: 1.09, 95%CI: 1.05-1.13, P < 0.001) than males. Females had a higher risk of all-cause mortality (RRR: 1.13, 95%CI: 1.07-1.19, P < 0.001), cardiac mortality (RRR: 1.49, 95%CI: 1.11-2.00, P = 0.009) and CHD mortality (RRR: 1.44, 95%CI: 1.20-1.73, P < 0.001) as compared to males. CONCLUSIONS: This umbrella review demonstrates that females with T2DM have a higher risk of cardiovascular outcomes than their male counterparts. Future research should address the basis of this heterogeneity and epidemiological factors for better quality of evidence, and identify actionable interventions that will narrow these sex disparities.

This umbrella review highlights the sex differences in adverse cardiovascular events in patients with type 2 diabetes mellitus (T2DM), with females at a higher risk than males. This is contributed by both biological and healthcare disparities and underscores the need for equitable care and personalized medical therapy.Females with T2DM have a higher risk of coronary heart disease, acute coronary syndrome, heart failure, and cardiac mortality compared to males.Clinicians need to be aware of the substantial heterogeneity across the current T2DM studies, and future meta-analysis and large-scale studies examining sex differences in outcomes should attempt to address the heterogeneity and epidemiological factors for a better quality of evidence.